Numerous medical conditions are caused by the existence and/or proliferation of unwanted or undesirable cells within a patient. Such conditions include cardiovascular ailments, such as a trial fibrillation and in-stent restenosis of coronary arteries, arteriovenous vascular malformations (AVMs), cardiac arrhythmias, Parkinson's disease, orthopedic ailments, such as post-op ossification, degenerative and inflammatory arthritis and bone spurs, wet macular degeneration, endocrine disorders, such as insulinomas and pituitary adenomas, herniated or inflamed discs, ovary-related conditions, Graves opthalmoplegia, dermatological ailments, such as furunclosis, telangiectasia, Kaposi's sarcoma, genito-urinary conditions, and cancer.
More specifically, cancer is caused by the altered regulation of cell proliferation, resulting in the abnormal and deadly formation of cancer cells and spread of tumors. Cells are the basic building blocks and fundamental functioning units of animals, such as human beings. Each cell is composed of a nucleus, which contains chromosomes, surrounded by cytoplasm contained within a cell membrane. Most cells divide by a process called mitosis. While normal cells have functioning restraints that limit the timing and extent of cell division, cancerous cells do not have such functioning restraints and keep dividing to an extent beyond that which is necessary for proper cell repair or replacement. This cell proliferation eventually produces a detectable lump or mass herein referred to as a tumor. If not successfully treated, it can kill the animal host.
Cancer that initiates in a single cell, and causes a tumor localized in a specific region, can spread to other parts of the body by direct extension or through the blood stream or lymphatic vessels, which drain the tumor-bearing areas of the body and converge into regional sites containing nests of lymph nodes. The ability of cancer cells to invade into adjacent tissue and spread to distant sites (metastasize) is dependent upon having access to a blood supply. As such, tumors larger than 2 mm have a network of blood vessels growing into them, which can be highly fragile and susceptible to breakage.
Several general categories of cancer exist. Carcinomas are cancers arising from epithelial (squamous cell carcinoma) or secretory surfaces (adenocarcinomas); sarcomas are cancers arising within supporting structures such as bone, muscle, cartilage, fat or fibrous tissue; hematological malignancies are cancers arising from blood cell elements such as leukemia lymphoma and myeloma. Other cancers include brain cancers, nerve cancers, melanomas, and germ cell cancers (testicular and ovarian cancers). Carcinomas are the most common types of cancers and include lung, breast, prostate, gastrointestinal, skin, cervix, oral, kidney and bladder cancer. The most frequently diagnosed cancer in men is prostate cancer; in women it is breast cancer. The lifetime risk of a person developing cancer is about 2 in 5 with the risk of death from cancer being about 1 in 5.
Diagnosing cancer often involves the detection of an unusual mass within the body, usually through some imaging process such as X-ray, Magnetic Resonance Imaging (MRI), or Computed Tomography (CT) scanning, followed by the surgical removal of a specimen of that mass (biopsy) and examination by a pathologist who examines the specimen to determine if it is cancer and, if so, the type of cancer. Positron Emission Tomography (PET) can be used to non-invasively detect abnormally high glucose metabolic activity in tissue areas and thereby assist in the detection of some cancers. The cancer is then assigned a stage that refers to the extent of the cancer. Each cancer has a staging protocol designated by organ. Conventionally, Stage I indicates the existence of a detectable tumor under a specified size, depending on cancer type. Stage II indicates that the cancer has spread into adjacent tissue or lymph nodes. Stage III indicates that the cancer has spread beyond its own region or has grown to a minimum size qualifying it for Stage III status, and Stage IV indicates that the cancer involves another organ(s) at a distant site. Stages are typically assigned by physical examination, radiographic imaging, clinical laboratory data, or sometimes by exploratory surgery.
Once diagnosed and identified in terms of characteristics, location, and stage, the cancer is treated using one, or a combination of several, methods, including surgery, chemotherapy, and radiation. Other less commonly used treatment approaches do exist, including immunotherapy. The cancer is treated with one or several basic goals in mind: cure, prevention of spread, prolongation of survival, and/or palliation (symptom relief).
Surgery is currently a preferred treatment approach where the cancer is localized, in an early stage, and present in only one place. Preferably, the cancer is within a substantial margin of normal tissue and can be excised without unacceptable morbidity or incurring the risk of death. Moreover, for surgery to be successful, the cancer should have little potential to spread to other parts of the body. Surgery needs to be followed up by diagnostic imaging to determine if the cancer has been removed and, in many cases, subsequent adjuvant radiation and/or chemotherapy is administered.
Chemotherapy, usually employing medicines that are toxic to cancer cells, is given by injection into the blood stream or by pill. With certain limitations, the chemotherapeutic agents travel to all parts of the body and can treat cancer in any location by interfering with cell division. Although affecting cancer cells to a greater extent, chemotherapeutic agents do interfere with normal cell division as well, causing severe side effects and adverse health consequences to patients, such as kidney failure, severe diarrheas, or respiratory problems. Certain agents are highly toxic to the heart, reproductive organs, and/or nerves. Almost all are toxic to the bone marrow, which is responsible for the production of the white and the red blood cells and platelets. Because white blood cells such as granulocytes, monocytes and lymphocytes, are primarily responsible for fighting infections and platelets are essential for clotting, chemotherapeutic agents often cause patients to be highly susceptible to infections and spontaneous bleeding. Other side effects include nausea and ulcerations. The course of chemotherapy requires a number of dosage cycles to attack cancer cells, permit healthy cells to recover, and then again attack the target cancer cells. Depending on the patient's response, a decision is made to either stop treatment or continue with some sort of maintenance dosage.
Radiation therapy is the exposing of cancerous cells to ionizing radiation with the objective of terminating those cells over one or several division cycles. Conventionally, radiation is delivered by sending an energy beam, typically x-rays, through a pathway containing healthy tissue and into the target cancerous region. Because energy is being driven through healthy tissue, medical practitioners must determine the best way to deliver sufficient energy to kill a plurality of cancerous cells without generating unacceptable levels of collateral damage to adjacent normal tissue. Several factors should be taken into account, including, for example: 1) the energy deposition profile, which determines what amount of energy a particular radiation beam, having a particular energy level, will deliver to the pathway relative to the target cancer cells, 2) the amount of energy needed to terminate cancerous cells, which determines the threshold level of energy that needs to be delivered to the target site and, consequently, what amount of collateral damage may have to be tolerated in order to do so, and 3) the size, shape, and location of the tumor, which is used to calculate the requisite radiation dosage and determine the appropriate configurations by which radiation beams can be delivered to the target site.
Conventional radiation therapies are frequently unable to deliver sufficiently high levels of radiation to a target region without generating unacceptably high levels of collateral damage. The most common radiation therapy, x-ray (or photon), has a linear energy transfer (LET) profile that varies with depth. The LET of photon radiation increases initially and then decreases with depth, often depositing more energy in intervening tissue than in the target tumor site for deeply buried targets. Photons also continue traveling through the body, once they pass the target region, further depositing energy in healthy tissue. Photons are therefore unable to precisely target a tumor region without endangering surrounding normal tissues.
As such, x-ray radiation treatment sequentially delivers small doses of radiation (fractions) capable of terminating cancerous cells without inflicting too much damage on normal cells. Dividing cells are more susceptible to radiation damage; non-dividing (i.e. resting cells) are less susceptible. X-ray radiation is very often delivered using multiple fields which are required to avoid repeatedly exposing a single healthy tissue pathway to lethal radiation. For example, a typical treatment regimen may require 20-25 exposures in which 200 RADS (Radiation Adsorbed Dose) are delivered per day, 5 days per week for 5 weeks, resulting in a total dose of 5,000 RADS, or 50 Grays, where several of those exposures occur through different pathways having the same target region, an isocenter, in common. Frequent radiation treatments (fractionation of dose) need to occur over a large portion of the replication cycle of a particular cancer, explaining the basis for why a series of treatments over several weeks is required to treat cancer with photon radiation therapy. It should be noted that, even with treatment fractionation and using multiple dose delivery pathways, the collateral damage causes substantial adverse health consequences, from nausea and pain to the permanent disruption of mucosal linings surfaces and adjacent supporting structures.
Proton therapy is another form of radiation therapy currently being used to treat cancer. Relative to other conventional approaches, protons have improved physical properties for radiation therapy because, as a radiation source, they are amenable to control, and thus the radiation oncologist can more precisely shape dose distribution inside a patient's body. Therefore, the dose delivered by a proton beam may be better localized in space relative to conventional radiation therapies, both in the lateral direction and in depth, causing more destruction at a target site with correspondingly less collateral damage.
As shown in FIG. 1, where the target tumor site is at a depth of 25 cm, a mono-energetic proton beam 110 deposits the same energy dosage as a beam of photon energy 105 at the target point. However, the collateral damage, represented by the difference 115, 120 in the areas under the curves between the energy dosages of the two respective beams 110, 105 (measured in areas outside the target region 125), is far greater for the photon beam 105. As a result, the proton beam 110 delivers the same termination power at the tumor site with correspondingly less collateral damage.
A substantial amount of investment has been made in researching proton therapies and building and deploying a proton therapy infrastructure, including proton accelerators, proton delivery devices, such as proton gantries, and specialized medical facilities. Despite this substantial investment, proton therapy still has several significant disadvantages. Most significantly, while the energy deposition profile in proton radiation represents an improvement over conventional approaches, it still does not deliver sufficient amount of termination power at a tumor site relative to the collateral damage it causes.
Another cancer therapy, heavy ion therapy, uses a heavy ion, namely an atom (e.g., a carbon atom) that has been stripped of its electrons, to deliver cancer cell terminating energy to a target region. Like proton beam therapy, heavy ion therapy has the ability to deposit energy directly into the cancerous tumor in three dimensions, hence the dose delivered by the heavy ion beam may also be better localized in space relative to conventional radiation therapies both in lateral direction and in depth. Heavy ions deposit more energy into a tumor than do protons and hence have more cancer cell killing capability than do protons. Heavy ions do have the capability of killing resting cells, but while the killing power deposited on the tumor for ion therapy is dramatically greater, the collateral damage to healthy intervening tissue (that issue between the skin surface and the tumor) is likewise greater—even greater collateral damage than for conventional radiation. In fact, collateral damage inflicted by heavy ion therapy can be even greater than the direct damage to the tumor with proton therapy. Additionally, in certain heavy ion therapy applications, treatment imaging is enabled by the fragmentation of the heavy ion, such as .sup.12C, as it approaches a patient in-beam and as it strikes cells while traveling through a patient. The heavy ion fragments into isotopes that may be imaged through conventional PET detection, that being .sup.11C in the case of .sup.12C heavy ion therapy. This imaging process is not, however, real-time in that imaging is delayed until the radioisotope decays and is substantially complicated by the migration of the isotope within the tumor.